Citation

Carlson SW, Yan HQ, Ma X, Li Y, Henchir JJ, Dixon CE. J. Neurotrauma 2015; 33(1): 113-121.

Affiliation

University of Pittsburgh, Neurosurgery, Pittsburgh, Pennsylvania, United States ; carlsons@pitt.edu.

Copyright

(Copyright © 2015, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2014.3839

PMID

25923735

Abstract

Traumatic brain injury (TBI) impairs neuronal function and can culminate in lasting cognitive impairment. While impaired neurotransmitter release has been well established after experimental TBI, little is understood about the mechanisms underlying this consequence. In the synapse, vesicular docking and neurotransmitter release requires the formation of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. Impairments in vesicle docking, and alterations in SNARE complex formation are associated with impaired neurotransmitter release. We hypothesized that TBI reduces SNARE complex formation and disrupts synaptic vesicle distribution in the hippocampus. To examine the effect of TBI on the SNARE complex, rats were subjected to controlled cortical impact (CCI) or sham injury and the brains were assessed at 6 hours, 1 day, 1, 2, or 4 weeks post-injury. Immunoblotting of hippocampal homogenates revealed significantly reduced SNARE complex formation at 1 and 2 weeks post-injury. To assess synaptic vesicles distribution, rats received CCI or sham injury, and the brains were processed for transmission electron microscopy at 1 week post-injury. Synapses in the hippocampus were imaged at 100k magnification, and vesicle distribution was assessed in pre-synaptic terminals at the active zone. CCI resulted in a significant reduction in vesicle number within 150 nm of the active zone. These findings provide the first evidence of TBI-induced impairments in synaptic vesicle docking, and suggest that reductions in the pool of readily releasable vesicles and impaired SNARE complex formation are two novel mechanisms contributing to impaired neurotransmission after TBI.

Language: en